Evaluation of 3D bioprinted hiPSC-derived astrocytes' reactivity and dedifferentiation

• Grant number: 22/06554-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: December 21, 2022
• End date: December 20, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Marimélia Aparecida Porcionatto
• Grantee: Elisa Marozzi Cruz
• Supervisor: Francis Szele
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: University of Oxford, England
• Associated to the scholarship: 20/12454-0 - 3D bioprinting of reactive astrocyte-derived neural stem cells, BP.DR

Abstract

Current in vitro models of the Central Nervous System (CNS) present several limitations regarding poor representation of three-dimensional (3D) environments and as so, fail to reproduce the tissue's dynamics in health and disease. As an alternative to two-dimensional (2D) cell cultures, 3D bioprinting represents a new technology to produce artificial, tissue-like structures with the possibility of microenvironment modulation. The neurogenic potential of the adult CNS is restricted to neural stem cells found primarily in the canonical neurogenic niches of the CNS, characterizing the limited regeneration potential of the nervous tissue. More recently, several authors described that reactive astrocytes can produce neural stem cells, both in vitro and in vivo. Astrocytes make up a heterogeneous population with different capacities to generate stem cells after activation, which is an indication of a promising intrinsic neurogenic program within the adult CNS. Our laboratory developed a protocol for 3D bioprinting of astrocytes derived from mice brain. The evaluation of reactive astrocytes' behavior within 3D bioprinted constructs is unprecedented and the assessment of astrocytic dedifferentiation and neuronal differentiation focusing on the activation of astrocytes' neurogenic potential could provide new data on injury recovery and neural tissue modulation. In this proposal we aim to evaluate the neuronal differentiation potential of 3D bioprinted reactive astrocytes derived from human induced pluripotent stem cells (h-iPSC). (AU)